Pharmacology L5 Flashcards
How do drugs work
- drugs must exert some
chemical influence on one or more constituents of cells - there must be non-uniform distribution of drugs within the body
- they interact with specific binding sites to modify the physiological/ biochemical state of cells, tissues and organs
Major targets of drug action are
-Hormones
-Ion channels
-Carriers
-Enzymes
- Membrane receptors
- Nuclear receptors
- DNA
What are the levels of drug action
MOLECULAR
CELLULAR
TISSUE
SYSTEM
Molecular level of drug action
Biomolecules as immediate targets of drugs
Cellular level of drug action
Biochemical constituents in the process of transduction
Tissue level of drug action
Alters organ function
System level of drug action
Alters system function
How do drug-receptor interactions occur
through reversible non-covalent bonds
Drug-receptor interactions
- Highly stable ion-ion electrostatic attraction
- Partial charge dipole-ion electrostatic
- Partial charge dipole-dipole electrostatic
- Low strength van de Waals’ electrostatic attraction between apolar groups
- Hydrophobic interactions of apolar molecules in an aqueous environment
How do most drugs exert their properties
by binding protein domains
Protein targets for drug binding
- Receptors
- Ion channels
- Carrier
- Enzymes
Specificity of drug action
reciprocal or dose-dependent
Reciprocal drug action
Some drugs bind only to certain molecular and cellular targets. Certain molecular and cellular targets recognize only certain classes of drugs.
Dose-dependent specificity of drug action
Increasing the dose of drug will affect molecular targets other than the principal pharmacological one, causing toxic side-effects.
What is an Agonist
Drug that binds and activates its respective receptor.
What is affinity
Tendency of a drug to bind to a receptor.
Receptor occupation by drug is governed by affinity.
What is efficacy
Tendency of a drug, once bound, to activate the receptor. Receptor activation by bound drug is governed by efficacy
What is an antagonist
Drug that binds to receptor without triggering activation, thus preventing binding of agonist/physiological ligand.
What is a Maximal pharmacological response
The maximal response on a particular receptor differs between chemically
related agonists
What is a maximal response
The largest response that a tissue can give
if triggered by a specific substance at high concentration.
Why is the therapeutic dose of a drug sometimes lower then its maximal response dose
Due to toxic side effects
What is a log-dose response used for
to quantify the relationship between biological responses and agonist concentration
What is a full agonist
A drug that can produce a maximal response
What is a partial agonist
A drug that can only trigger a sub-maximal response.
What happens if a tissue contains a receptor reserve due to poor intrinsic efficacy
allows partial agonist to act as a full agonist.
What is a receptor reserve
agonist only needs to activate a smaller number of receptors than the total number available to produce a maximal response
what is intrinsic efficacy
the ability of a drug- receptor complex to produce a maximal response
What is a competitive agonist
Substance that has no intrinsic efficacy and binds reversibly with receptor. It dilutes the receptor concentration. Importantly, an increase of agonist dose can return tissue response to normal. (uses up receptor that agonist can use, can be removed)
What is an irreversible agonist
Causes blocking of a receptor that cannot be reversed by increasing the agonist concentration. high concentrations of agonist leads to depression of the maximum response.
Function of agonistic versus antagonistic blocking action
in Nicotinic acetylcholine receptor (nAChR)
Skeletal muscles are relaxed during surgical procedures by using neuromuscular drugs (agonists/ antagonists) to cause clinical paralysis of voluntary muscles.
What is the competitive antagonist that can function in nAChR
Tubocurarine
How does Tubocurarine function as an antagonist
It competes with the native ligand neurotransmitter acetylcholine for the receptor. However, it does not cause a biological response
What is the agonist that functions in nAChR
Suxamethonium
How does Suxamethonium work
It depolarizes the neuromuscular junction but does not dissociate rapidly from the nAChR complex causing a neuromuscular block
Molecular approaches used in the structural analysis of pharmacologically important protein receptors
¤ Protein purification and characterization
¤ Affinity purification and characterization
¤ Protein/peptide N-terminal sequence analysis
¤ Mass spectrometric analysis of protein subunits
¤ Cloning and sequencing of cDNA
¤ High-resolution x-ray crystallography
¤ High-resolution cryo-electron microscopy
¤ Differential co-immuno precipitation methodology
¤ Chemical cross-linking analysis
¤ Native two-dimensional gel electrophoresis
¤ Gel filtration analysis
